Rational Design, Synthesis, and Biological Evaluation of Progesterone-Modified MRI Contrast Agents

Jiyoun Lee; Joanna E. Burdette; Keith W. MacRenaris; Devkumar Mustafi; Teresa K. Woodruff; Thomas J. Meade

doi:10.1016/j.chembiol.2007.06.006

Rational Design, Synthesis, and Biological Evaluation of Progesterone-Modified MRI Contrast Agents

Jiyoun Lee, Joanna E. Burdette, Keith W. MacRenaris, Devkumar Mustafi, Teresa K. Woodruff, Thomas J. Meade^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

A series of contrast agents for magnetic resonance imaging (MRI) aimed at noninvasively determining the hormone receptor status of cancer in vitro was developed. These MRI contrast agents were prepared by conjugating progesterone to clinically used Gd(III) chelates. These agents exhibited higher progesterone receptor binding affinities in the nanomolar range and intracellular accumulation. High logP values of the modified compounds suggested that the lipophilicity of the steroid conjugates may have contributed to membrane permeability. Synchrotron radiation X-ray fluorescence microscopy and magnetic resonance images revealed that the synthesized conjugates showed the greatest cellular accumulation and significant increase in relaxivity in vitro compared to the previously developed steroid-modified agent. Transcriptional assays using the progesterone response element linked to luciferase indicated that the contrast agents entered the cell, interacted with the biological target, and drove specific progesterone-mediated transcription.

Original language	English (US)
Pages (from-to)	824-834
Number of pages	11
Journal	Chemistry and Biology
Volume	14
Issue number	7
DOIs	https://doi.org/10.1016/j.chembiol.2007.06.006
State	Published - Jul 30 2007

Keywords

CHEMBIOL

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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abstract = "A series of contrast agents for magnetic resonance imaging (MRI) aimed at noninvasively determining the hormone receptor status of cancer in vitro was developed. These MRI contrast agents were prepared by conjugating progesterone to clinically used Gd(III) chelates. These agents exhibited higher progesterone receptor binding affinities in the nanomolar range and intracellular accumulation. High logP values of the modified compounds suggested that the lipophilicity of the steroid conjugates may have contributed to membrane permeability. Synchrotron radiation X-ray fluorescence microscopy and magnetic resonance images revealed that the synthesized conjugates showed the greatest cellular accumulation and significant increase in relaxivity in vitro compared to the previously developed steroid-modified agent. Transcriptional assays using the progesterone response element linked to luciferase indicated that the contrast agents entered the cell, interacted with the biological target, and drove specific progesterone-mediated transcription.",

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author = "Jiyoun Lee and Burdette, {Joanna E.} and MacRenaris, {Keith W.} and Devkumar Mustafi and Woodruff, {Teresa K.} and Meade, {Thomas J.}",

note = "Funding Information: We gratefully acknowledge National Institutes of Health grants 1 R01 EB005866-01 (T.J.M.), NIH 5 U54 CA90810 (T.J.M.), and R01 HD044464 (T.K.W.) for support of this work. ",

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AU - Woodruff, Teresa K.

AU - Meade, Thomas J.

N1 - Funding Information: We gratefully acknowledge National Institutes of Health grants 1 R01 EB005866-01 (T.J.M.), NIH 5 U54 CA90810 (T.J.M.), and R01 HD044464 (T.K.W.) for support of this work.

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Rational Design, Synthesis, and Biological Evaluation of Progesterone-Modified MRI Contrast Agents

Abstract

Keywords

ASJC Scopus subject areas

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